ION PAIR ALDOL ADDITION REACTIONS

描述：主要研究者指出，添加羟醛 反应是形成碳-碳键的最重要的反应之一 在合成有机化学反应，它被广泛用于 药物和其他生物活性分子的合成， 反应现在最常在非极性溶剂中进行，例如 四氢呋喃（THF），经常与羰基锂盐 化合物（烯醇化锂）。 他报告说， 化合物已通过溶液性质，NMR和X射线表征 晶体学，这种聚集体已被提出作为 羟醛型加成反应中的活性物种与其他羰基 衍生物，但很少有研究的实际作用， 反应中的聚集体。 他继续指出，通过组合 紫外可见光谱和质子转移平衡研究的一些 锂烯醇化物，聚集常数已获得，即使在 稀释溶液和光谱作为浓度函数， 通过“奇异值分解”分析，以确定 不同的物种存在，并允许去卷积，以给出 各组分的光谱。 为此，手套箱光谱仪 已经开发了一种装置，其中样品室内置于 手套箱通过光缆与光谱仪连接。 应注意，该装置允许溶液的光谱分析 在手套箱的惰性气氛下制备和研究。 的 迄今为止的结果表明，单体离子对可能 在反应中起着重要的动力学作用。 建议将此类研究扩展到其他感兴趣的烯醇化物 并测量其Aldol加成反应动力学， 醛和酮的Michael加成反应以及与不饱和烃的Michael加成反应 羰基化合物 动力学研究表明， 烯醇化物反应性物质的聚集状态， 离子对单体和聚集体的相对作用的知识将 导致更完整的反应机制和更好的 理解复杂的合成设计所需的。 校长 研究人员特别注意到，溶剂粘合剂的作用， 例如锂盐、六甲基磷酰三胺和二-和 三胺将在仔细控制的条件下进行研究， 确定锂在立体化学中的配位作用 加成反应。 还建议应用光谱研究的相同技术， Aldol和Michael的质子转移平衡和反应动力学 羧酸和β-二锂盐的加成反应， 二酮。 应注意，这些二锂盐也可用于 在有机合成中的应用越来越多，但反应机理是 几乎无人研究。 据悉，这些盐类还聚集在 但对单体的相对反应性一无所知， 集料. 拟议的研究将提供独特的信息 关于这些反应，这将是很难获得在任何其他 路上了 建议随后扩展到其他碱金属盐 和碱土金属，早期和晚期过渡金属， 还提出了镧系元素，因为这些盐中的许多已经发现用于 在某些立体定向合成中。

DESCRIPTION: The principal investigator notes that the Aldol addition reaction is one of the most important carbon-carbon bond forming reactions in synthetic organic chemistry, that it is widely used in the synthesis of drugs and other biologically active molecules and that the reaction is now most often run in non-polar solvents, such as tetrahydrofuran (THF), frequently with lithium salts of carbonyl compounds (lithium enolates). He reports that the aggregation of these compounds has been characterized by solution properties, NMR and by X-ray crystallography and that such aggregates have been proposed as the reactive species in the Aldol-type additions with other carbonyl derivatives but there have been very few studies on the actual role of such aggregates in reactions. He goes on to note that by a combination of UV-vis spectroscopic and proton transfer equilibrium studies of some lithium enolates, aggregation constants have been obtained even in dilute solution and that spectra as a function of concentration are analyzed by "Singular Value Decomposition" to determine the number of different species present and to permit deconvolution to give the spectrum of each component. For this purpose a glovebox-spectrometer apparatus has been developed in which the sample compartment built into the glovebox is connected with a spectrometer with fiber-optic cables. It is noted that the apparatus permits spectroscopy of solutions prepared and studied under the inert atmosphere of the glovebox. The results thus far are said to suggest that the monomeric ion pairs might play an important kinetic role in reactions. It is proposed to extend such studies to additional enolates of interest and to measure the reaction kinetics of their Aldol additions to aldehydes and ketones and of Michael addition reactions with unsaturated carbonyl compounds. It is indicated that the kinetic studies will show the state of aggregation of the enolate reactive species and that knowledge of the relative roles of ion pair monomers and aggregates will lead to more complete reaction mechanisms and to the better understanding required for sophisticated synthesis design. The principal investigator notes that in particular, the roles of solvent addends, such as lithium salts, hexamethylphosphoric triamide, and di- and triamines will be studied under carefully controlled conditions to determine the role of coordination of lithium in the stereochemistry of the addition reactions. It is also proposed to apply the same techniques of spectroscopic study, proton transfer equilibria and reaction kinetics of Aldol and Michael addition reactions to the dilithium salts of carboxylic acids and beta- diketones. It is noted that these dilithium salts are also being used increasingly in organic synthesis but that the reaction mechanisms are virtually unstudied. It is reported that these salts are also aggregated but nothing is known about the relative reactivities of monomers and aggregates. The proposed studies are to provide unique information about these reactions, which would be difficult to obtain in any other way. It is suggested that subsequent extension to other salts of alkali and alkaline earth metals, early and late transition metals and lanthanides is also proposed since many of these salts have found use in some stereospecific syntheses.